Variant 4-83421744-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The NM_133636.5(HELQ):c.2776-8C>G variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000197 in 1,608,546 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00099 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00011 ( 0 hom. )

Consequence

HELQ
NM_133636.5 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.08137

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.60

Variant links:

Genes affected

HELQ (HGNC:18536): (helicase, POLQ like) HEL308 is a single-stranded DNA-dependent ATPase and DNA helicase (Marini and Wood, 2002 [PubMed 11751861]).[supplied by OMIM, Mar 2008]

HELQ links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.39).

BP6

Variant 4-83421744-G-C is Benign according to our data. Variant chr4-83421744-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 3040053.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
HELQ	NM_133636.5 linkuse as main transcript	c.2776-8C>G	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	ENST00000295488.8
HELQ	NM_001297755.2 linkuse as main transcript	c.2575-8C>G	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant
HELQ	NM_001297756.2 linkuse as main transcript	c.1285-8C>G	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant
HELQ	NM_001297757.2 linkuse as main transcript	c.1144-8C>G	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris	UniProt
HELQ	ENST00000295488.8 linkuse as main transcript	c.2776-8C>G	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	1	NM_133636.5	P1	Q8TDG4-1
HELQ	ENST00000510985.1 linkuse as main transcript	c.2575-8C>G	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	1
HELQ	ENST00000508591.5 linkuse as main transcript	c.*1208-8C>G	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, NMD_transcript_variant	1
HELQ	ENST00000512539.1 linkuse as main transcript	n.264-8C>G	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant	3

Frequencies

GnomAD3 genomes

AF:

0.000993

AC:

151

AN:

152138

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00345

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000459

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000286

AC:

AN:

244972

Hom.:

AF XY:

0.000264

AC XY:

AN XY:

132628

show subpopulations

Gnomad AFR exome

AF:

0.00381

Gnomad AMR exome

AF:

0.000214

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000900

Gnomad OTH exome

AF:

0.000167

GnomAD4 exome

AF:

0.000114

AC:

166

AN:

1456290

Hom.:

Cov.:

AF XY:

0.0000994

AC XY:

AN XY:

724538

show subpopulations

Gnomad4 AFR exome

AF:

0.00425

Gnomad4 AMR exome

AF:

0.000208

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.000183

GnomAD4 genome

AF:

0.000992

AC:

151

AN:

152256

Hom.:

Cov.:

AF XY:

0.000833

AC XY:

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.00344

Gnomad4 AMR

AF:

0.000458

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000335

Hom.:

Bravo

AF:

0.00143

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

HELQ-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 28, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.39

Cadd

Benign

Dann

Benign

0.75

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.081

dbscSNV1_RF

Benign

0.29

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over